ClinVar Miner

Submissions for variant NM_000530.8(MPZ):c.487G>A (p.Gly163Arg) (rs281865128)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneReviews RCV000193606 SCV000243905 pathogenic Charcot-Marie-Tooth disease, demyelinating, type 1b 2015-03-26 no assertion criteria provided literature only
Inherited Neuropathy Consortium RCV000789471 SCV000928827 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only
Invitae RCV000538322 SCV000636250 pathogenic Charcot-Marie-Tooth disease, type I 2017-04-05 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 163 of the MPZ protein (p.Gly163Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with Charcot-Marie-Tooth type 1 (CMT1) (PMID: 8800924) as well as in three members of a family affected with CMT1 (PMID: 27088055). ClinVar contains an entry for this variant (Variation ID: 208148). A different variant (c.487G>C) giving rise to the same protein effect observed here (p.Gly163Arg) has been reported to segregate with disease in two families affected with CMT1 (PMID: 12207932, 15170620), indicating that this residue may be critical for protein function. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic.

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